The invention relates to 10-bromosandwicine and 10-isobromosandwicine, methods for preparing same and pharmaceutical compositions thereof, and their use as chemical intermediates.
Sandwicine is an indole alkaloid from the group of rauwolfia alkaloids. This alkaloid is described in detail by M. Gorman et al, Tetrahedron 1, (1957) pp. 328-337. It is an isomer of the rauwolfia alkaloid ajmaline. Ajmaline and its isomer isoajmaline have been known to possess cardiac activities including antiarrhythmic activities. 10-bromoajmaline also is known to possess cardiac activities (see Petter et al, Arch. Expt. Pathol. Pharmakol. 243, 519-527 (1962)). However from what is known in the art about the cardiac activities of bromoajmaline it can be concluded that the pharmacological profile of ajmaline and its antiarrhythmic activity were not improved by bromination, yet there is in indication of a tendency towards an increase of harmful side effects (see Voelkner et al Z. ges. exp. Med. 1135, 330-354 (1962)).
Contrary to ajmaline no significant antiarrhythmic activities could be detected for sandwicine and isosandwicine in a standard pharmacological in vivo test procedure.
Quarternary salts of ajmaline and isoajmaline are known to possess valuable pharmaceutical properties in particular antiarrhythmic properties. A well known representative of these known quarternary ajmaline and isoajmaline derivatives is a mixture of N.sub.b -propylajmalinum and N.sub.b -propylisoajmalinium hydrogentartrate which is the active ingredient of an antiarrhythmic pharmaceutical composition which is commercially available under the tradename Neo-Gilurytmal.RTM. and is used in the treatment of disorders in the coronary and circulatory system, especially heart rhythm disorders.
From German Offenlegungsschrift No. 26 11 162 it is known that N.sub.b -quarternary derivatives of sandwicine and isosandwicine exhibit valuable pharmacological properties, in particular heart rhythm regulating properties and are useful in the treatment of disorders in the coronary and circulatory system.
It is known that quarternary derivatives of ajmaline, isoajmaline, sandwicine and isosandwicine in addition to their desirable pharmacological properties also possess some undesirable side effects, e.g. negative inotropic properties and sedative side effects.